Some substances with confirmed carcinogenic activity do not react in the Ames test for carcinogenesis, viz., they do not react with DNA. Among these is ethionine which does not react with DNA, but does react with transfer RNA. The latter reaction is specific for a minor species of tRNA, tRNA2Lys. This selectivity implies the intervention of some enzymes which recognize tRNALys. In addition, we have discovered that administration of ethionine elevates progesterone levels in the target animal. The elevation is extraordinarily high; it can be as high as ten-fold. In addition to ethionine, two other carcinogens which are negative in the Ames test, actinomycin D and thioacetamide also elevate progesterone levels. The aim of this research project is to study the molecular mechanisms of this novel mechanism of carcinogenesis.